Anemia has become increasingly recognized as a major contributor to morbidity and mortality in the elderly. Although it is clear that anemia is an independent risk factor associated with reduced survival in patients over age 65, the etiology of anemia in at least one third of these patients is unknown, as is the pathogenesis by which it leads to physical decline and death. A better understanding of the pathophysiology of anemia in the elderly, with attention to the contribution of co-morbid disease, both primary hematologic and nonhematologic comorbidities, should provide critical entry points for interventions that will improve survival and quality of life in the elderly population. The Veterans Aging Cohort Study (VACS) is an observational study of 3,213 veterans with and 3,161 demographically similar veterans without HIV infection. The database includes full electronic medical record data and annual self-completed surveys on all subjects. Subsets have participated in telephone interviews, patient and provider focus groups, and tissue collection. A large substudy has also been initiated for blood and DMA banking. Over 65% of VACS subjects are black or Latino and the median age is 50 years. Because the Veterans Health Administration (VHA) is a largely closed system of care, we enjoy near complete data collection and follow-up. VHA provides substantial support for this project including housing, datasets, informatics, teleconferencing, and assistance with data cleaning, and storage. This study has already provided important data confirming that anemia is an independent risk factor for death in both the HIV+ and HIV- patient populations. Interestingly, the hazards ratio is highest in both groups for those patients with macrocytosis, although it seems quite possible that the causes of an elevated MCV in these two groups could be divergent. Both aging and HIV are associated with elevation in the level of circulating cytokines that are associated with frailty, namely TNF and IL-6. Chronic inflammation has also been linked with polymorphisms affecting levels of macrophage migration inhibitory factor (MIF) gene, which induces TNF. Our central hypothesis is that in the absence of nutritional deficiency, anemia in the elderly usually reflects a proinflammatory state with an associated anemia of inflammation. We would suggest that HIV induces a frail state similar to that seen in the elderly with a more frequent and earlier anemia that reflects an acceleration of the inflammatory process associated with aging. Our specific aims are: [unreadable] [unreadable] 1. To characterize the age-stratified etiology of anemia in the cohort population. 2. To characterize the role of a chronic proinflammatory state in the age-stratified incidence of anemia. 3. To characterize the role of genetic polymorphisms in predicting the development of a proinflammatory state. [unreadable] [unreadable] [unreadable]